1. Field of the Invention
The present invention relates to a manufacturing method of an organoboron compound. An organoboron compound obtained by using the manufacturing method is widely used as a reactant in organic synthesis, such as a reaction in which the organoboron compound diastereoselectively reacts with a carbonyl compound to produce a homoallylic alcohol.
2. Description of Related Art
Since an allylboron compound diastereoselectively reacts with a carbonyl compound to produce a homoallylic alcohol, it is well known as a useful reactant in organic synthesis. For example, by reacting with an aldehyde, an anti-homoallylic alcohol can be obtained from an (E)-allylboron compound, and a syn-homoallylic alcohol can be synthesized from a (Z)-allylboron compound.
An optically active allylboron compound also can similarly selectively allylate a carbonyl compound under a moderate condition, and, along with a chiral transformation, produce an optically active homoallylic alcohol, and therefore, is a useful reactant. However, in an existing synthesis method, a super-stoichiometric amount of chiral auxiliary is required, and, in addition, a multi-step synthesis is required (Related Art 1). On the other hand, there is practically no example of synthesizing an optically active allylboron compound by using a catalytic chiral synthesis, except a relatively special example of diborylating an allene compound by using an optically active palladium catalyst (Related Art 2). The two examples are both difficult to be applied to the case of a compound having a complicated skeleton or the case of a functionalized compound.
Separately from the above-mentioned technologies, a selective synthesis method of synthesizing an allylboron compound from an allyl carbonate ester and a diboron has been developed that uses a copper (I) phosphine complex catalyst (Related Art 3). In this reaction, a boron substituent is selectively introduced at a γ-position with respect to an elimination group. In the case where an optically active allyl carbonate ester is used, along with a highly efficient chiral transformation, an optically active allylboron compound can be efficiently synthesized. This method is a useful method that enables selective synthesis of an allylboron compound having a functional group and a polysubstituted allylboron compound, which are so far difficult to synthesize. However, since an optically active allyl carbonate ester is required, there has been no report that an optically active allylboron compound has been synthesized from starting material having no optically active component.
Separately from an allylboron compound, a cyclopropane skeleton is a structure that is widely found in natural products, functional materials such as a liquid crystal, and organic compounds. In particular, natural products having cyclopropane rings, and their derivatives have attracted the interests of many Japanese and international scientists, with respect to their pharmacological activity, biosynthesis, and chiral synthesis. This is an area of active research even after over 120 years since William Henry Perkin first synthesized a cyclopropane derivative in 1884.
Since most of natural products having cyclopropane skeletons have multiple chiral points in cyclopropane rings, their chiral syntheses are particularly important. At the present, the most used cyclopropane synthesis method is a technique that utilizes metal carbenoid generation such as the Simmons-Smith reaction. In the past 20 years, chiral synthesis has been further developed, and a technique utilizing a chiral auxiliary (Related Art 4) and an enantioselective technique utilizing a transition metal catalyst (Related Art 5) have been developed.
These techniques utilize double bonds that exist in a molecule to construct a cyclopropane ring. With regard to this, a method has been developed in recent years that utilizes a coupling reaction to directly introduce a pre-synthesized cyclopropane skeleton into a molecule. When a boryl cyclopropane having a boron substituent on a cyclopropane is synthesized, and is applied to the Suzuki-Miyaura coupling reaction that is widely used in organic synthesis, a product is obtained that has a cyclopropane skeleton introduced therein. So far, there have been research reports from multiple research groups (Related Art 4 and Related Art 6).
Here, when an optically active boryl cyclopropane can further be synthesized, it is possible to introduce an optically active cyclopropane skeleton. However, in this case, the issue is a more efficient synthesis of the optically active boryl cyclopropane.
So far reported optically active boryl cyclopropane synthesis methods can be broadly categorized as the following two techniques. First, an example of techniques that have been studied since some time ago is the technique that pre-introduces a chiral auxiliary group on boron, and utilizes carbenoid generation to diastereoselectively construct a cyclopropane ring (Related Art 7). On the other hand, an enantioselective hydroboration reaction with respect to a disubstituted cyclopropane utilizing a chiral catalyst was recently reported (Related Art 8). The synthesis that utilizes a chiral auxiliary agent requires an equal or larger amount of chiral source with respect to a substrate, and its selectivity is not extremely high. On the other hand, although the catalytic chiral synthesis is a useful technique in that a target product can be obtained from a small amount of chiral source with a high enantioselectivity, this is the only report about an optically active boryl cyclopropane, and it has a limitation with respect to applicable scope of the substrate, such as that it is limited to a substrate activated by an ester substituent.
[Related Art 1]Angew. Chem. Int. Ed. 25 (1986) 1028-1030.[Related Art 2]J. Am. Chem. Soc. 126 (2004) 16328-16329.[Related Art 3]J. Am. Chem. Soc. 127 (2005) 16034-16035.[Related Art 4]Tetrahedron Lett. 38 (1997) 2809-2812.[Related Art 5]Angew. Chem. Int. Ed. 41 (2002) 2953-2956.[Related Art 6]Synlett. 41 (1996) 893-895.[Related Art 7]J. Chem. Soc., Perkin Trans. 1 (2000) 4293-4300.[Related Art 8]J. Am. Chem. Soc. 125 (2003) 7198-7199.